Outside of orthomyxoviruses
- Simple on the outside
- Linear, - ssRNA
- Contain HA and NA surface proteins
Genome of orthomxoviruses
Have 6- different segments of genetic material, some coding for two things wit different reading frames or promoter sequences
Proteins of the genome
- Envelope glycoproteins: HA and NA
- integral membrane protien: (M2)
- Matrix protein (M1)
- Nucleocapsid (NP)
- nonstructural (NS1)
- minor structural (NS2
- additional non strutural (PB1-F2)
Genes and proteins
HA and NA are on two different gene segments
3 proteins deal with the interstructure of the virus. they are viral RNA dependent polymerases that are made of different subunits
What is the special case that must occur since it is negative sense
at least one copy of an RNA pol has to be packaged in
no polymerase= no infection
There was a recently discovered...
protein that can be made from PB2 segment
really short peptide that is an open reading frame and has specific immune system effects
Viruses and hosts
these viruses affect mucus tisse and make you cause and sneeze
Explain this: influenza has its own family tree
- all differ in the HA and NA
- A affects humans and mutates faster
- B affects humans and is a seasonal epidemic
A and B are genetically differetn
What sets influenza apart?
high fever, sore throat, cough, headache, muscular pain
incapacitation for about a week
can be fatal in the elderly, infants, and chronically ill; complications--> death
What is the trend for influenza?
a classic U-shaped curve with age and fatality on the x and y axis, respectively
at very young and old age, virus is deadly
this trend exists for the regular annual flu
Explain the two epidemics that were pretty bad
1918: pandemic= 20 millino people dead
2009: new strain; bird flu that threatened domestic fowl and humans
Explain the trend of the 1918-1919 pandemic
w shaped curve
it affected overall life expectancy
- more than 10,000 people died in a month
- US military men died more of the flu than in combat
- Everything else became secondary to surviving the infection
mortality rate spiked in Oct and Nov
rate of dying correlated to age; middle aged also at risk
The Fle: seasonal versus pandemic
seasonal: reliably, it kills alot of people and can be the number one killer of children in developing countries really affects young and elderly; fatality is 0.5%
pandemic: deaths can be 4-5%
Pandemic Influenza mortality
The 1918 virus was so frightening because one minute you were fine, the next, you were dead
Reasons for the pandemic
viral genes: some strains are worse in humans
WWI: lots of people in poor health and close quarters--> increased subsceptibility and transmission
Poor understanding of disease
successful for getting stains in those with Spanish flu
There was bacterial growth in the lungs of those infected, which usually caused the death
95% of people that died from flu had positive bacterial infection association
Bacteria may have evolved to take advantage of the niche
Stability of flu?
constantly mutating and changing, rendering immunity meaningless. Howver, it is cyclical
Explain the cyclical nature of flu.
IT comes and goes and comes back
People in 1918 saw a flu that was similar to something their bodies have previously encountered, rendering them somewhat immune--> decrease in mortality
- can take several forms
- 1) if growing in person= long and filamentous (quasi-spherical is what you see in lab; filamentous is what you see in person)
explain the different shapes of the virus?
filaments help it come in contact with another cell while it is budding from one host membrane, transmitting it to another cell
the spherical is how you can transmit to another person
Genes and proteins again
there is some space inside the virus around the genome segments, each of which has specific organizationa nd way of folding together
a spin, a cube, and then proteins
Three biggest genes?
encode the segments for polymerase
the smallest code for nonstructural
A nuclear protein which resembles a green ball is not different from other nuclear proteins and wraps the RNA, whih loops up and back down
Explain the polymerase
it is in three different subsets, each having its own polymerase that is bound to it and brought with it
PA, PB1, and PB2 all together wound up with loop structure and polymerase with it
Most important (to us) protein on the virus?
hemagglutinin protein: does both jobs that virus surface proteins need to do
- 1) mediates fusion in endosomes
- 2) binds to receptors
HA binds to...
a molecule called sialic acidin muclproteins
each HA binds to different sialic acids
What is hemagglutinin named after?
- ability to cause hemagglutination
- binds to RBCs, hemaggluniating agent causes RBCS to cross link and no longer clump and settle at the bottom. They stay in solution
What is good about hemagglutinin?
it is one of the most reliable sources of detecting infection
- 1) Take serum
- 2) Drop it in and mix with RBCS
- 2) If hemagglutination occurs, the virus is present
an ion channel that faciliates release of nucleocapsids from the virion
It allows the protons to enter the interior of the virus weakening the interaction of M1 with the nucleocapsids
Amantadine blocks the M2 channel
Unlike other RNA viruses, what does orthomyxo do?
it replicates in the nucleus, complicating the machinery required for viral replication
The capped 5' ends of cellualr pre-mRNAs are used as __.
- priers for synthesis of viral mRNAs
- inhibitors of cellular RNA synthesis also blocks virus replciation
It is a cap snatch
Viral mRNAs terminate in __.
poly(A) tail generated by "stuttering" transcription
Explain alternative splicing in relation to influenza
Two influenza A mRNAs undergo alternative splicing in the nucleus
- -- unspliced RNAs create M1 and NS1
- -- spliced RNAs create M2 and NS2
When does genome rep begin?
when newly synthesized NP protein enters the nucleus
replication of genome requires no primer
Nucleocapsids are __.
exported from the nucleus in a complex with matrix protein and NS2
The NS1 protein does what?
interferes with polyadenylation of cellular mRNAs
it binds to and blocks the function of cleavage and polymadenylation specificy factor (CPSF) and poly(A)-binding protein (PABII)
The NS1 protein also....
suppresses a variety of host cell antiviral response pathays
- 1) inhibits RIG-I
- 2) Activates P13K/Akt pathway
- 3) Inhibits PKR
- 4) Inhibits 2',5'-oligo(A) synthetaase/Ribonuclease L
may contribute in suppression of host immune response
localizes to mitochondria and induces apoptosis in host immune cells